rs201629827
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP6BS1
The NM_001382391.1(CSPP1):āc.3296A>Gā(p.Glu1099Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000663 in 1,613,646 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001382391.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CSPP1 | NM_001382391.1 | c.3296A>G | p.Glu1099Gly | missense_variant | Exon 29 of 31 | ENST00000678616.1 | NP_001369320.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CSPP1 | ENST00000678616.1 | c.3296A>G | p.Glu1099Gly | missense_variant | Exon 29 of 31 | NM_001382391.1 | ENSP00000504733.1 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152118Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000561 AC: 14AN: 249516Hom.: 0 AF XY: 0.0000739 AC XY: 10AN XY: 135372
GnomAD4 exome AF: 0.0000664 AC: 97AN: 1461410Hom.: 0 Cov.: 30 AF XY: 0.0000756 AC XY: 55AN XY: 727052
GnomAD4 genome AF: 0.0000657 AC: 10AN: 152236Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74444
ClinVar
Submissions by phenotype
Joubert syndrome 21 Uncertain:1Benign:1
This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 1094 of the CSPP1 protein (p.Glu1094Gly). This variant is present in population databases (rs201629827, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with CSPP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 510229). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
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not provided Uncertain:1Benign:1
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This variant is associated with the following publications: (PMID: 25616960, 30755392) -
CSPP1-related disorder Uncertain:1
The CSPP1 c.3281A>G variant is predicted to result in the amino acid substitution p.Glu1094Gly. This variant was reported as a heterozygous variant of uncertain significance with no second hit, in an individual diagnosed with Joubert syndrome (Ji et al. 2019. PubMed ID: 30755392). In ClinVar this alteration has conflicting classifications of uncertain and likely benign (https://www.ncbi.nlm.nih.gov/clinvar/variation/510229/evidence/). This variant is reported in 0.0098% of alleles in individuals of South Asian descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at